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Ahmed Kamal Virology Journal 2011, 8:532
http://www.virologyj.com/content/8/1/532

REVIEW

Open Access

Observations on rift valley fever virus and
vaccines in Egypt
Samia Ahmed Kamal

Abstract
Rift Valley Fever virus (RVFV, genus: Phlebovirus, family: Bunyaviridae), is an arbovirus which causes significant
morbidity and mortality in animals and humans. RVFV was introduced for the first time in Egypt in 1977. In
endemic areas, the insect vector control and vaccination is considering appropriate measures if applied properly
and the used vaccine is completely safe and the vaccination programs cover all the susceptible animals. Egypt is
importing livestock and camels from the African Horn & the Sudan for human consumption. The imported
livestock and camels were usually not vaccinated against RVFV. But in rare occasions, the imported livestock were
vaccinated but with unknown date of vaccination and the unvaccinated control contacts were unavailable for
laboratory investigations. Also, large number of the imported livestock and camels are often escaped slaughtering
for breeding which led to the spread of new strains of FMD and the introduction of RVFV from the enzootic
African countries. This article provide general picture about the present situation of RVFV in Egypt to help in
controlling this important disease.
Keywords: Rift Valley fever virus, RVFV, Inactivated RVF vaccines, MP12, Live attenuated RVF vaccines, Smithburn
strain.

Introduction
Rift Valley fever virus (RVFV, genus Phlebovirus and
family Bunyaviridae), was isolated from infected sheep in
1930 [1,2]. RVFV is an arbovirus that can be transmitted
directly (between vertebrates during the manipulation of
infected tissues, and between mosquitoes by vertical transmission) and indirectly (from one vertebrate to another by
mosquito-borne transmission) [3,4]. It is enveloped, segmented into three parts, single stranded RNA virus. The
three segments are; small (S), medium (M) and large (L).
The S segment is of ambisense polarity and encodes for
two proteins; nucleocapsid protein (N) that coats the viral
genome and a nonstructural protein (NSs). The NSs is a
filamentous nuclear protein, expressed by a virus that
replicates and assembles in the cytoplasm of infected cells.
The NSs protein has been identified as a major virulence
factor. The phosphoprotein NSs is not essential to viral
replication in tissue culture thus allowing clones carrying
deletions in NSs to predominate as they replicate more
rapidly [4]. The M segment encodes for two proteins
(NSm) of 14 kDa and 78 kDa and envelope glycoproteins

(G1 and G2) which play an important role in RVFV infection and pathogenesis [2]. The L segment encodes the
viral RNA-dependent RNA polymerase [5-8].
RVFV is a dose dependant pathogen. Whenever, the
dose of RVFV was decreased, the onset of the disease and
the time of death were delayed [9]. RVFV has only one
serotype [10], but strains exist of variable virulence [11].
This genetic stability is assumed to result from a fitness
trade-off imposed by host alternation, which constrains
arbovirus genome evolution. Otherwise, no genetic
changes were found in viruses that were passaged alternately between arthropod and vertebrate cells. Furthermore, alternating passaged viruses presenting complete
NSs gene remained virulent after 30 passages. Therefore,
alternating replication is necessary to maintain the virulence factor carried by the NSs phosphoprotein [4].
RVFV causes a significant threat to both human and animal health [12]. It was recorded that during periods in
which human epidemics arise they are preceded by epizootics in livestock. These livestock epizootics serve as an
amplification step in the spread of the virus. Prevention of
disease in animals through the use of safe and effective

Correspondence: selkabany@yahoo.com
Virology department, Animal Health Research Institute, Dokki, Giza, Egypt
© 2011 Kamal; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.

Ahmed Kamal Virology Journal 2011, 8:532
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vaccine would serve to prevent human disease by breaking
the amplification cycle [13].

The endemic status of RVFV in Egypt
According to the facts that most arthropod-borne viruses
(arboviruses) are RNA viruses, which are maintained in
nature by replication cycles that alternate between arthropod and vertebrate hosts [4]. RVFV ability to persist in
nature depends upon certain factors which are present in
Egypt [14]. These factors are: 1- the presence of unvaccinated susceptible livestock, camels and wild animals in
large number over large areas, would play the major role
in the ability of RVFV to establish the endemic cycle
[15,16], 2- the presence of suitable environmental conditions for the insect vector propagation in the absence of
effective vector control programs. 3- The vaccination with
RVF live attenuated vaccines (Smithburn’s strains) plays
important role in the persistence of this endemicity in
Egypt because it contaminate the environment and transmitted by insect vector [17]. 4- The vaccination programs
were alternating between the killed and the live vaccines,
the latter was used before, during or after the outbreaks in
unidentified manner. 5- The vaccination by the inactivated
vaccines is not covering all the susceptible animals. 6- The
human losses in the first RVFV in 1977 were massive as a
result of the lack or absence of public health education
beside the delay in announcing the problem and delay of
control programs. However, these social and medical
situations are not changed till the present time. 7- The
geographical continuity with Africa and the Sudan, and
the Nile River facilitate the continuous introduction of
infected livestock, camel or wild animals. 8- The importation of livestock from the horn of Africa and the Sudan
which are enzootic countries. The government of Egypt
instructions for importing live animals was to slaughter
them upon arrival. Contrarily, these importing animals are
usually mixed with the native breeds and moving freely in
different localities of the country. 8- The field trials performed by different scientific institutions in Egypt are not
under control, and participate in the environmental contaminations with the live vaccinal strains.
Inter-epizootic periods
The scientific data about the inter-epizootic periods of
RVFV in Egypt are missed. However, researches provide
us by some important information. In 1987, some investigator recorded the presence of a mild form of RVF disease
circulating as a sub-clinical infection among animals in
Sharqyia Governorate as atypical RVF epidemic or epizootic [18]. Other study was described the pathological picture of RVF on suspected heifers from Friesian dairy farm
with a history of abortion in 1989 [19]. Meanwhile, in a
study of the prevalence of antibodies to RVFV in 915 persons in the Nile river delta of Egypt, the IgG antibody to

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RVF virus was detected in 15% of specimens in 1993 [20].
AHRI mentioned in an official report about RVF situation
in Egypt that RVFV was isolated from limited numbers of
native animals in Keina governorate of Upper Egypt in
1996 and in Damitta governorate of Nile Delta of Egypt in
2003 (AHRI, personal communication). In like manner,
NAMRU-3 has been reported that it was played a key role
in the outbreak investigations in Egypt in 1996 and 2003
[21].
Also, during year 2000, 4,161 serum samples were collected from different Governorates 1-6 months post vaccination with inactivated vaccine, a total of 977 cattle, 743
buffaloes, 1,127 sheep and 1,314 goats. The infectivity for
each species ranged from 5.78, 9.58, 12.28 and 13.59 for
goat, sheep, cattle, and buffalo respectively. The infectivity
percentage in some animals indicates that the virus still
circulating in the presence of the insect vector. The susceptibility of different species (animals have neither IgM
nor IgG) were 13.11%. Sheep showed low susceptibility by
9.41%, indicating the concentration of vaccination program on sheep. Some animals were escaped vaccination
and others showed immune-suppressive diseases [22].
Largest RVFV outbreaks in Egypt
The 1st outbreak 1977-1978

The first outbreak of RVF in Egypt was recorded at Sharqiya Governorate in October 1977. The outbreak first
appeared in man as an acute, febrile, dengue-like illness in
Sharqiya Governorate in Egypt. Then, RVFV was isolated
from man at the virus Research Center, Agousa district in
Cairo and characterized as an Arbovirus. This isolate (isolate no. 41) was confirmed as RVFV at the WHO collaborating center for Reference and Research on Arbovirus
Disease at Yale Arbovirus Research Unit (YARU), USA
[17,18]. However, the veterinarians who were sharing in
controlling this early outbreak in 1977, stated that RVF
entered Egypt for the first time by the Egyptian troops
who came back after peace keeping mission in the Congo
and the outbreak in animals and human began at the
same place of these infected troops in Belbies city, Sharqiya Governorate [Safi Al-Din Sakr, GOVS, Sharqiya
branch, personal communication] [19].
As a matter of fact, during periods in which human
epidemics arise they are preceded by epizootics in livestock. These livestock epizootics serve as an amplification
step in the spread of the virus. This outbreak indicated
that man can serve as RVFV amplified subject. This can
be achieved by the circulation of the virus between insect
vector and other vertebrates in the human dwellings.
Additionally, there are some controversies in recording
for this important outbreak. Some reports stated that
RVFV probably introduced in Egypt by importing
infected sheep and camels [20,21]. Other investigations
mentioned that during the epidemic of RVF that

Ahmed Kamal Virology Journal 2011, 8:532
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occurred in Egypt and other areas of North Africa in
1977, the virus was isolated from various species of
domestic animals and rats (Rattus rattus frugivorus) as
well as man. Also, the highest numbers of RVFV isolates
were obtained from sheep; only one isolate was recovered
from each of the other species tested, viz. cow, camel,
goat, horse, and rat.
The human losses in this outbreak were massive. The
lack of previous medical experience about RVF patients
and the insufficient health education programs considered
principal factors in this concern. Likewise, the host innate
immune response plays a major role in RVF host resistance. Therefore, hepatic affections are predispose to the
severity of the illness in Egyptian farmers who suffering
Schistosomiasis, HCV, HBV, HCC and Cirrhosis. As well
as, infants, very young children and immune compromised
patients are more liable to RVFV.
The 2nd outbreak 1993

The source of RVFV in this outbreak was probably due to
natural infection or vaccinal strains. It was recorded that
the Egyptian RVFV isolates group contains strains isolated
in 1977 and 1993 epidemics, was appeared in the phylogeny as sister groups. This finding was suggesting that
either the virus remained endemic between the two outbreaks or have been reintroduced in 1993 from the same
source (probably Sudan) as in 1977 [22]. However, some
studies were suggested that the virus was reintroduced
through an incompletely inactivated RVF veterinary vaccine [23]. However, this outbreak probably was due to
post-vaccinal reactions with reversion to virulence of the
vaccinal strain. During 1993, the AHRI mission was
reporting RVF in governmental farms, located in North of
Egypt (Damitta Governorate). These farms were vaccinated by RVF attenuated vaccine 20 days prior to the
onset of the disease [the author was a member of this mission]. The pregnant cows, adults, and calves were suffering
severe illness, mortalities and a storm of abortion following vaccination with the live attenuated RVF vaccine
(Smithburn strain). This live vaccine was imported by the
Egyptian General Organization for Veterinary Services
(GOVS) from the South Africa (Veterinary Research Institute, Onderstepoort, 01100 South Africa, Batch No.G119
in terms of Act 36 of 1947). The exact reason for importing this vaccine is unknown either the real date or place of
first vaccination or field trials in Egypt.
The 3rd outbreak 1994

During 1994, RVFV was isolated from the infected cattle
and sheep in Behera and Kafr el Sheikh Governorates The
serological investigations revealed 31.65% and 57.1% prevalence of virus in 139 cattle and 84 sheep, respectively.
The locally produced live attenuated RVF vaccine, Smithburn strain, was officially applied for use in Egypt the
same year (Batch No. 1-1994) [24]. This outbreak showed
the failure of the locally applied RVF vaccination program

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with both the imported and the locally produced live attenuated vaccine (Smithburn strain).
The 4th outbreak 1997

At the beginning of the summer of 1997, a high incidence
of abortion was observed among pregnant sheep and cattle
with high mortalities in young lambs and calves during the
summer of 1997 in Upper Egypt. The disease was more
severe in sheep than in cattle and in young animals than
in adults. The abortion rate in pregnant ewes was approximately 60%-70% and in pregnant cows approximately
30%-40%. A mortality rate of approximately 50%-60% was
recorded in young lambs, 25%-35% in adult sheep, 25%30% in calves and 10%-20% in adult cattle. This study
reveals massive infections and indicated the absence of an
effective traceability system in Egypt [25].
Also, during 1997, a concurrent infection of Theileriosis
and RVFV among calves and cattle in dairy farm were
reported. The affected farm which located in Assiut governorate, Upper Egypt was containing both native cattle
(110) and Holstein Friesian (104) [26].
These findings reveal the failure of vaccination programs
by the live RVF vaccines. Despite, RVFV is characterized
by the presence of inter-epizootic periods of 10-15 years,
this outbreak occurred a 3 years only after the last epizootic in 1994. Additionally, RVFV infections under natural
conditions are usually subside and the herd acquired solid
immunity until a naïve herd present in sufficient numbers.
This unusual behavior of the virus was probably a postvaccinal reaction of the live vacinal strains (Smithburn
strain) beside the continuous importation of infected
ruminants, especially camels from enzootic areas in Africa
[25].
The 5th outbreak 2003

The biggest market of livestock in Egypt located in Kafr el
Sheikh Governorate, about 150 km north of Cairo, where
animals are collected from all over the country. Such
environment predisposed to another RVFV outbreak during year 2003. This outbreak was encountered in different
localities of Egypt [27]. The RVF disease in human probably was owned to the direct contact with infected animals, or through infected droplets during the slaughtering
of sick cattle, or through bites of mosquitoes fed on
infected blood. The farmers are usually slaughtering the
sick animals, resulting in the spread of the highly amplified
virulent RVFV in the surroundings. In similar manner,
students at a South African veterinary college, several
veterinarians and veterinary staff were infected after handling and performing necropsies on animals that were only
later identified as infected with RVF virus [28,29].
Thus human infection seems inevitable during RVF epizootics. RVFV amplification cycles in livestock frequently
precede human cases by 34 weeks, and play a critical role
in the early stages of an outbreak. The highly viraemic
(virus circulated in blood) animals serve as an excellent

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source of direct contamination of humans, as well as a
blood meal source for mosquitoes which can transmit the
virus to humans [30]. The same finding was obtained by
the analysis of livestock and human data in the RVFV outbreak in Kenya (2006 and 2007) which suggests livestock
infections would be occurred before virus detection in
humans [31].
In spite of the severe epidemic, the Egyptian Ministry
of Agriculture refuses to announce this epizootic till the
present time. However, as of 28 August 2003, WHO
received reports of 45 cases of Rift Valley fever (RVF)
including 17 deaths in Seedy Salim district, a remote
rural area in Kafr Al-Sheikh governorate, about150 km
north of Cairo. All cases are Egyptian farmers. Laboratory testing carried out at the Naval Medical Research
Unit No.3 (NAMRU-3), Cairo, has confirmed the diagnosis of RVF in clinical samples. A gradual increase in
the number of suspected cases of RVF in Seedy Salim
district has been reported as a result of active surveillance [32].
The RVFV was isolated by AHRI from a veterinary
samples collected from Damitta Governorate during
year 2003 (AHRI, personal communication). Recently
the scientific data regarding this outbreak was referred
to the spread of RVF all over the country. In June, 2003,
Egypt’s hospital-based electronic disease surveillance
system began to record increased cases of acute febrile
illness from governorates in the Nile Delta. In response
to a request for assistance from the Egyptian Ministry of
Health and the World Health Organization (WHO), the
U.S. Naval Medical Research Unit No. 3 (NAMRU-3)
provided assistance in identifying the cause and extent
of this outbreak. Testing of human clinical samples (n =
375) from nine governorates in Egypt identified 29 cases
of RVF viraemia that spanned the period of June to
October, and a particular focus of disease in Kafr el
Sheikh governorate (7.7% RVF infection rate). Veterinary
samples (n = 101) collected during this time in Kafr el
Sheikh Governorate (Egypt) and screened by immunoassay for RVFV-specific IgM identified probable recent
infections in cattle (10.4%) and sheep (5%). Entomologic
investigations identified three isolates of RVF virus
(RVFV) from 297 tested pools of female mosquitoes and
all three RVFV isolates came from Cx. antennatus
(Becker). This is the first time that Cx. antennatus has
been found naturally infected with RVFV in Egypt [27]
Table 1).

The role of camels in RVFV transmission
Camels are multipurpose domestic animals used for
meat, hair and hide production beside transportation.
Also, camels play certain role in the continuous introduction of RVFV in Egypt. On the contrary to the OIE rules,
camels enter Egypt officially without any virological

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investigation, and even without maintaining for sufficient
period in the quarantine facilities. The GOVS consider
the long distance the animals spent walking is enough for
judging that they are free from the viral infections. In reality, this is not matched the OIE rules for importing live
animals.
The continuous importation of viraemic ruminants,
especially camels, from the Sudan was the main source
of infection in RVF and FMD outbreaks in Egypt [25].
Furthermore, RVFV infections are due to live animal’s
importation. However, the importation from Africa consider of high risk due to the presence of trans-boundary
animal diseases (TADs) such as Rift Valley Fever and
Foot and Mouth Disease (FMD), with the absence of an
effective traceability system that acts as proxy for quality
assurance [33].
Serologic evidence of RVF in camels is frequently
reported. Widespread abortion waves in camels were
observed during RVF outbreaks in Kenya and Egypt.
Camels are suspected of playing a major role in the
spread of RVF from northern Sudan to southern Egypt in
1977. Also, RVF virus was previously isolated from blood
samples from healthy, naturally infected camels in Egypt
and Sudan. Although, RVFV susceptibility varied from
species to another, some virulent strains could change
the classic picture of the epizootics. This was observed
during September-October 2010, when an unprecedented
outbreak of Rift Valley fever was reported in the northern
Sahelian region of Mauritania after exceptionally heavy
rainfall. Camels probably played a central role in the local
amplification of the virus. During this outbreak, two clinical forms were observed in camels: Peracute form, with
sudden death in less than 24 h; and acute form with
fever, various systemic lesions and abortions. When
hemorrhagic signs developed, death usually occurred
within a few days in manner resembles infections in the
most susceptible species (sheep) [34].

RVF vaccines used in Egypt
Currently, there are no licensed vaccines for RVF that are
both safe and efficacious for human use. The following
vaccines are for veterinary use only: 1- Live attenuated
Smithburn strains, produced by VSVRI, 2- Formalin inactivated, alum adjuvanted, (Menya/Sheep/258) produced by
VACSERA, 3- Binary ethylenamine inactivated (ZH501
RVF strain) and Alum adjuvanted, which produced by
VSVRI.
Control of RVF in Egypt depends mainly on periodical
vector control and vaccination of susceptible animals with
binary inactivated RVF vaccine. Smithburn’s neurotropic
attenuated RVFV strain is a 104th intracerebral passage in
baby mice followed by two passages in baby hamster kidney cell line. It was 10 7.5 TCID 50/ml. However, questions

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Table 1 RVFV outbreaks in Egypt
Year

Vaccines

Characteristics

1977-1978

No vaccination

RVFV introduced from Africa by infected persons back from
Africa & animals from the Sudan, probably viraemic camels.
Showed historic massive human losses.
Led to the establishment of the endemic state.
RVFV isolation from infected humans and animals

1993-1994

Live attenuated
(Smithburn strain),
Used during
the outbreak

Epizootic and Epidemic. Probably natural infections, beside
Vaccinal strains.
Source of virus from the Sudan by infected ruminants.
Infections encountered in all Egyptian Governorates.

1996-1997

Live attenuated
(Smithburn strain),
Used during
the outbreak

Epizootic and Epidemic. Source of data: literatures, OIE, NAMRU-3
Cairo. Showed human infections among some farmers and veterinarians.
Indicate the failure of the applied vaccination programs.
Showed failure of general authority to face the real situation.
Questionable traceability of the GOVS, *AHRI, *VSVRI.
Importation of infected animals without proper laboratory tests.

2003

Live attenuated
(Smithburn strain),
Used during
the outbreak

Epizootic and Epidemic. Encountered in Nile Delta &
Upper Egypt Governorates. Source of data:
WHO, NAMRU-3 Cairo, Literatures.
Many human losses among farmers. Massive losses in animals.
Indicate the failure of the applied vaccination programs.
Indicate failure of general authority to face the real situation.
Questionable traceability of the GOVS, *AHRI, *VSVRI

*Animal Health Research Institute (AHRI). *Veterinary Serum &Vaccine Research Institute (VSVRI)

exist concerning the abortogenicity and teratogenicity of
the preparation as well as its phenotypic stability [35].
The description of the live attenuated RVF vaccine
(smithburn strain) which produced by the Egyptian VSVRI
stated the following; a- Live attenuated freeze dried tissue
culture Rift Valley Fever virus vaccine (smithburn strain).
b- The vaccine contains 104 TCID 50/ml. RVFV. c- The
virus grows on tissue culture cell line. d- It is indicated for
the protection of sheep and goat against Rift Valley Fever
disease. e- The vaccine not used for pregnant animals as
the vaccine may cause abortion or embryo abnormalities.
f- The dosage and method of use; 1- the content of the
vaccine vial dissolved in 100 ml. 2- sterile distilled water
or physiological saline.3- each animal can be vaccinated by
1 ml s/c. 4- Sheep and goat should be vaccinated at 4
months of age. Remarks: 1- Avoid exposure of the vaccine
to direct sunlight and heat. 2-Clinically ill animals should
not be vaccinated.3- Do not vaccinate animals during
breeding season of mosquitoes. 4- Animals used for
human consumption should not be slaughtered within 21
days after vaccination. 5- Used syringes, needles and
remaining vaccine in bottles should be disposed hygienically. The vaccine should be stored at - 20°C. Expire date
is 2 years from the date of manufacture [36].
In the light of this description we can realize how much
this vaccine is unsafe. It is for use in sheep and goats
only. As a fact, the mosquito’s breeding season in Egypt
is 12 month per year because of the warm winter and the
other ecological and environmental factors. However, the
safety requirements of using it in the absence of mosquito, as mosquitos present anywhere and anytime of the

year make it impractical for general use. The vaccinated
animals shouldn’t be slaughtered within 21 days after
vaccination, because of viraemia. In experimental study
performed by VSVRI and NARU-3, a number of 318
cows and 115 buffaloes were vaccinated with the locally
prepared RVF Smithburn vaccine, of which, 100 cows
and 20 buffaloes were pregnant. Twenty eight pregnant
cows were aborted within 72 days post-vaccination. Buffaloes didn’t abort. RVFV was isolated from one aborted
fetus. Moreover, the antibody response to vaccination
with local Smithburn strain had occured in some, but not
all the cows and buffaloes. Virus isolation from the fetus
suggests in utero transmission of the used vaccinal strain,
which resulted in high abortions in cows [37].
Field study was carried out in Alexandria, Egypt, to
assess the use of locally produced inactivated and attenuated Rift Valley fever (RVF) vaccines on lambs and calves.
The study recommends the usage of RVF inactivated vaccine because it was safe and gave results as live attenuated
vaccine especially with a poster dose after 5 months of the
first vaccination [38].

Discussion
RVFV is endemic in Africa and Arabian Peninsula [39].
This virus is classified as a high-consequence pathogen
with the potential for international spread (List A) by the
World Organization for Animal Health (Office International des Epizooties) [40]. The disease is fatal in man
with unhealthy liver and immunocompromised patients
are more liable to the disease. RVF control in animals
through the use of safe and effective vaccine will prevent

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the human disease by breaking the amplification cycle
[41].
RVF virus amplification cycles in livestock frequently
precede human cases by 34 weeks, and play a critical
role in the early stages of an outbreak. These highly viraemic (virus circulated in blood) animals serve as an
excellent source of direct contamination of humans, as
well as a blood meal source for mosquitoes which can
transmit the virus to humans [42].
In the present time, Egypt is importing Camels, cattle,
and small ruminants from the horn of African & the
Sudan which are not vaccinated against RVFV. However,
in case of importation from countries which vaccinate
against RVFV, the imported animals were with no date of
vaccination and the unvaccinated control contacts were
unavailable for further veterinary investigations. The regulatory plan for livestock importation was to slaughter
these animals upon their arrival for human consumption.
Some of these animals usually escaped slaughtering for
breeding which led to the spread of new strains of FMD
and introduction of RVFV from enzootic areas. However,
the vaccination programs by killed vaccines only which
applied by Ministry of Agriculture have been limiting to
great extent the possibilities of RVFV outbreaks in Egypt.
Control of RVF disease in Egypt depends mainly on
vaccination of cattle, sheep and goats. Two types of formalin inactivated RVF vaccines were produced in Egypt;
first produced by VACSERA company which is formalin
inactivated & alum adjuvanted (Menya/Sheep/258), and
the second produced by the Veterinary Serum and Vaccine Research Institute (VSVRI) which is binary ethylenimine (BEI) inactivated & alum adjuvanted (ZH501
strain) [43,44].
The live attenuated RVF Smithburn vaccine also referred
as Smithburn neurotropic strain or SNS. The Smithburn
neurotropic strain of RVF virus was derived from the virulent Entebbe strain by numerous serial intracerebral passages in mice [45]. This live vaccine was imported from
South Africa and subsequently produced by VSVRI
according to protocol of WHO/FAO (1983) [46].
In the light of the use of live attenuated RVF vaccine
(smithburn strain) for animals consider of high risk as it
causes abortion in pregnant animals, teratogenic effects
and the reversion to be virulent is possible. The VSVRI
stopped producing the live attenuated RVF vaccine
(Smithburn strain) as the Rift Valley fever department,
was reported the possibility of the vaccinal strain reversion
to virulence state [37,44,47,48].
As has been noted in a research studies performed in
VSVRI, the RVF live vaccine adverse effects were illustrated [37,47,48]. They mentioned that a locally inactivated RVF vaccine was produced for vaccination of cattle
and sheep. The inactivated vaccine was still used until the
appearance of the outbreak in Egypt in 1993. The general

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authority uses the imported RVF attenuated vaccine
(smithburn strain) to overcome this problem. Yet, a locally
attenuated RVF vaccine was produced from Smithburn
strain in 1994 (modified live virus vaccine MLVV). This
attenuated vaccine was used together with the inactivated
one for vaccination of farm animals, but the live virus vaccine may cause abortion, and its potential for reversion to
virulence has not been adequately investigated [37,47].
They added, WHO/FAO meeting (1983) warranted the
use of such attenuated vaccine as there are major practical and theoretical reasons for not using a live vaccine in
non-endemic RVF zones and in some endemic zones.
Lambs immunized at less than 6 weeks of age have a low
incidence of encephalitis and ewes immunized shortly
before giving birth may produce lambs with encephalitis.
In addition, MLVV induces abortion in a small percentage of pregnant ewes and may cause fetal abnormalities.
Also, the FAO meeting added that there is a theoretical
objection to use of a live attenuated vaccine, since such
vaccine might revert to virulence for cattle, sheep or
man. Moreover, the live vaccine has the capacity to cause
viraemia in vaccinated sheep, and therefore, arthropods
feeding on these animals may become infected and transmit the disease to domestic animals or man. They conclude that despite the disadvantages of the Smithburn
RVFV attenuated vaccine, their study explores another
disadvantage as the RVFV appeared in bull’s semen 1
week after their vaccination with the attenuated RVF vaccine with an average titre of 1 ELISA unit. Also, RVFV
was detected till the third week post-vaccination, and the
semen quality was severely affected. Thus, vaccination of
bulls with this attenuated RVF vaccine leads to dissemination of RVFV via semen as if they were infected, and
the use of these bulls for insemination might be of danger, somehow to these bulls as well as the inseminated
cows [47].
Vaccination with live attenuated vaccine was applied in
Egypt at intermittent periods, since the 1977 outbreak,
and killed vaccine was used for pregnant and young animals [44,47]. The Egyptian GOVS in 2008 mentioned that
RVF live vaccine (Smithburn strain) don’t used in Arab
Republic of Egypt in the present time. Consequently, the
RVF vaccination programs in Egypt are performed by the
killed vaccines only [44].
MP12 was invented by serial mutagenesis which was
undertaken with the Egyptian ZH501 and ZH548 strains
of RVF virus. Strain ZH501, which was received as a
first-passage virus grown in foetal rhesus monkey lung
(FRL) cells, originally came from the serum of a fatal haemorrhagic case of human RVF that occurred in the Sharqiya Governorate during the Egyptian outbreak of RVF in
1977. Strain ZH548, which was received after two passages in suckling mice and one in FRL cells, was recovered originally from the serum of an uncomplicated

Ahmed Kamal Virology Journal 2011, 8:532
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human febrile case of RVF that occurred in the same area
of Egypt. A total of 18 serial mutageneses were undertaken with ZH501, and 16 with ZH548. Mutagenesis consisted of growth of virus in the presence of 5-fluorouracil
(5FU) [49].
However, some studies showed that MP12 strain replicated in and was transmitted by female C. pipens after
intrathoracic inoculation [50]. Also, It was reported that
MP12 was evaluated in a group of 50 sheep at various
stages of pregnancy was inoculated with the virus and the
pregnancies followed to term. There were two abortions
and 14% of the lambs produced by vaccinated ewes
showed teratogenic effects, the most prevalent being spinal
hypoplasia, hydranencephaly, brachygnathia inferior and
arthrygryposis. The fetal malformations of the central nervous and musculoskeletal systems were mostly consistent
with those observed in sheep vaccinated with the attenuated Smithburn RVF strain [51].
The Egyptian General Organization of Veterinary Services (GOVS) policy of using inactivated vaccine (only) is
a candidate to change. A recent project of the GOVS of
Egypt is working to test the attenuated live vaccine MP-12
for possibility of its production and usage in Egypt. This
project is collaboration with NAMRU-3. They reports on
a project that is testing a vaccine developed by the U.S.
Army, called MP-12, on Egyptian domestic animals. This
project, collaboration with the Veterinary Serum and Vaccine Research Institute of the Egyptian Ministry of Agriculture and the U.S. Department of Agriculture is
studying how well this vaccine works. It is one of the most
promising vaccines to date, and if effective, could be tested
in the field in Egypt [21].
In addition to the disadvantages of using live vaccines,
some literatures also revealed that RVF MP12 strain is not
safe for using in endemic countries as Egypt. It was mentioned that to assess the genetic variability of Rift Valley
fever virus (RVFV), several isolates from diverse localities
of Africa were investigated by means of reverse transcription-PCR followed by direct sequencing of a region of the
small (S), medium (M), and large (L) genomic segments.
Phylogenetic analysis showed the existence of three major
lineages corresponding to geographic variants from West
Africa, Egypt, and Central-East Africa. However, incongruence detected between the L, M, and S phylogenies suggested that genetic exchange via reassortment occurred
between strains from different lineages. This hypothesis,
depicted by parallel phylogenies, was further confirmed by
statistical tests. These findings, which strongly suggest
exchanges between strains from areas of endemicity in
West and East Africa, strengthen the potential existence of
a sylvatic cycle in the tropical rain forest. This also emphasizes the risk of generating uncontrolled chimeric viruses
by using live attenuated vaccines in areas of endemicity
[52].

Page 7 of 9

The mutations responsible for attenuation of RVFV
have been examined by analysis of reassortant viruses
generated between the vaccine strain and a wild RVFV
strain isolated in Senegal. Their findings indicate that
genetic reassortment with wild-type viruses during a vaccination program in endemic areas would also be
expected to yield attenuated variants [53].
New strains of live attenuated RVFV are created by
using reverse genetics that is missing one or more viral
virulence factors, which facilitating the studies of viral
pathogenesis and the development of specifically attenuated vaccine strains. This system has been used to generate viruses that are missing the NSs protein, the NSm
protein, or both. In addition, unlike the currently available
attenuated strains, the ΔNSm/ΔNSs vaccine meets the
DIVA requirement by virtue of the missing NSs protein
[13].
Unfortunately, in spite of vaccination is frequently
believed to be an innocuous procedure, it is important to
recognize that vaccines can cause adverse reactions, as
vaccination is a serious medical act. However, recombination between live vaccinal strains and virulent strains is
possible under specific conditions, and may result in reversion to virulence of recombinant DNA (rDNA) vaccines or
conventional vaccines. Furthermore, vaccines marked by
the deletion of a gene can regain the deleted gene, with
dramatic consequences for eradication program [54].

Conclusions
The importation of animals infected with RVF from the
Sudan and failure of the locally applied RVF vaccination
program were the main causes of the reoccurrence of RVF
epizootics in Egypt. Continued outbreaks of RVF among
domestic ruminants, in 1977, 1978 and 1993, 1994, 1996,
1997, and 2003 indicate that the virus has become enzootic in Egypt. To control the disease in Egypt, some investigators suggest the following measures: - prevention of
introduction of ruminants infected with RVF, especially
camels, from northern Sudan into southern Egypt (Aswan
Province) - avoiding importation of ruminants from countries where RVF is enzootic - annual vaccination of all
ruminants (camels, cattle, buffaloes, sheep and goats) with
an effective RVF vaccine - trials for control of insect vectors - the intensive broadcast of educational television programs to inform farmers and owners about the
importance of vaccination programs [25].
Two live attenuated viruses have been tested in various
animals, a mutagen-attenuated strain (MP12) and the live
attenuated Smithburn strain. The results of these studies
with live vaccines are varied, in some instances showing
no clinical illness and the development of neutralizing
antibody titers as well as protection from challenge, and
in other studies showing the viruses to be abortogenic
and teratogenic. Therefore neither of these virus strains

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appears to be an ideal candidate for a vaccine strain
because of their questionable safety profiles, in addition
to their lack of DIVA capability [13].
Under those circumstances, it could be concluded that
the use of inactivated RVFV vaccine is safe and effective
in controlling RVFV especially when the vaccination
programs is strictly applied and cover all domestic animals in Egypt.
Authors’ contributions
SAK conceived of the study, and participated in its design and coordination.
The author read and approved the final manuscript.
Competing interests
The author declares that they have no competing interests.
Received: 19 April 2011 Accepted: 12 December 2011
Published: 12 December 2011
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doi:10.1186/1743-422X-8-532
Cite this article as: Ahmed Kamal: Observations on rift valley fever virus
and vaccines in Egypt. Virology Journal 2011 8:532.

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